Background Oral cancers account for approximately 2% of all cancers diagnosed each year; however, the vast majority (80%) of the affected individuals are smokers whose risk of developing a lesion is ve to nine times greater than that of non-smokers. Tobacco smoke contains numerous carcinogens that cause DNA damage, including oxidative lesions that are removed effectively by the base-excision repair (BER) pathway, in which poly (ADP-ribose) polymerase 1 (PARP-1), plays key roles. Genetic variations in the genes encoding DNA repair enzymes may alter their functions. Several studies reported mixed effects on the association between PARP-1 variants and the risk of cancer development. Till now no reported studies have investigated the association between PARP-1 variants and oral squamous cell carcinoma (OSCC) risk in an Indian population. Materials and Methods In the present case control study 100 OSCC patients and 100 matched controls were genotyped using PARP1 Single nucleotide peptides (SNP's) rs1136410 and rs3219090 using TaqMan assays. Results The results indicated signi cantly higher risk with PARP1 rs1136410 minor allele "C" (OR1.909; p0.02942; CI, 1.060- 3.439). SNP rs1136410 also showed signi cantly increased risk in patients with smoking habit at C/C genotype and at minor allele C. Conclusions The PAPR-1 Ala762Val polymorphism may play a role in progression of OSCC. Larger studies with more number of samples are needed to verify these ndings.